The structural basis for autoinhibition of FLT3 by the juxtamembrane domain

被引：401

作者：

Griffith, J ^{[1
]}

Black, J ^{[1
]}

Faerman, C ^{[1
]}

Swenson, L ^{[1
]}

Wynn, M ^{[1
]}

Lu, F ^{[1
]}

Lippke, J ^{[1
]}

Saxena, K ^{[1
]}

机构：

[1] Vertex Pharmaceut Inc, Cambridge, MA 02139 USA

来源：

MOLECULAR CELL | 2004年 / 13卷 / 02期

关键词：

D O I：

10.1016/S1097-2765(03)00505-7

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

FLT3 is a type III receptor tyrosine kinase that is thought to play a key role in hematopoiesis. Certain classes of FLT3 mutations cause constitutively activated forms of the receptor that are found insignificant numbers of patients with acute myelogenous leukemia (AML). The mutations occur either in the activation loop, for example, as point mutations of Asp835 or as internal tandem duplication (ITD) sequences in the juxtamembrane (JM) domain. To further understand the nature of FLT3 autoinhibition and regulation, we have determined the crystal structure of the autoinhibited form of FLT3. This structure shows the autoinhibitory conformation of a complete JM domain in this class of receptor tyrosine kinases. The detailed inhibitory mechanism of the JM domain is revealed, which is likely utilized by other members of type III receptor tyrosine kinases.

引用

页码：169 / 178

页数：10

共 58 条

[1] Identification of novel FLT-3 Asp835 mutations in adult acute myeloid leukaemia [J].